CAP Archives: Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors

José Manuel Naranjo Gómez, Jose Fernando Val Bernal, Pilar García Arranz, Servando Lazuén Fernández, and Jose Javier Gómez Roman (2014) Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors. Archives of Pathology & Laboratory Medicine: July 2014, Vol. 138, No. 7, pp. 936-942.

ORIGINAL ARTICLES

Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors

José Manuel Naranjo Gómez, MD, PhD; Jose Fernando Val Bernal, MD, PhD; Pilar García Arranz, MD; Servando LazuénFernández, MD; Jose Javier Gómez Roman, MD, PhD

From the Departments of Thoracic Surgery (Dr Naranjo Gómez) and Pathology (Drs Val Bernal, García Arranz, Lazuén Fernández, and Gómez Roman), Hospital Universitario Marqués de Valdecilla, Santander, Spain.

Context.—Neuroendocrine lung neoplasms are a heterogeneous group of tumors with different clinical behavior and prognosis.

Objectives.—To evaluate the expression of p53, KLF4, and p21 in neuroendocrine lung neoplasms and to analyze the influence that expression has on the prognosis of those tumors.

Design.—All neuroendocrine lung neoplasms (N = 109) resected in our institution were reviewed, with the collection of histologic slides and paraffin blocks of 47 typical carcinoids (43%), 9 atypical carcinoids (8%), 35 large cell neuroendocrine carcinomas (32%), and 18 small cell lung carcinomas (17%), as well as 10 tumorlets (100%). Four tissue microarrays were performed. Follow-up was assessed in all cases (119 of 119; 100%).

Results.—p53 protein immunostaining results were negative in both the tumorlets and typical carcinoids and were overexpressed in 11% (1 of 9) of the atypical carcinoids and in 68% (36 of 53) of the carcinomas. KLF4 results were positive in all tumorlets (10 of 10; 100%), 32% (15 of 47) of the typical carcinoids, 44% (4 of 9) of the atypical carcinoids, and 62% (33 of 53) of the carcinomas. p21 expression did not differ among the groups. The lack of KLF4 and p21 expression was associated with an accumulation of aggressive features in typical carcinoids (P = .04 and P = .004, respectively, Fisher exact test).

Conclusions.—p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids.